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Study of Intratumoral (IT) MK-1454 in Combination With Intravenous (IV) Pembrolizumab (MK-3475) Compared to IV Pembrolizumab Alone as the First Line Treatment of Metastatic or Unresectable, Recurrent Head and Neck Squamous Cell Carcinoma (HNSCC) (MK-1454-002)

NCT04220866

Description:

The purpose of this study is to assess the efficacy and safety of intratumoral (IT) MK-1454 in PLUS pembrolizumab (MK-3475) compared to pembrolizumab alone as a first line treatment of adults with metastatic or unresectable, recurrent head and neck squamous cell carcinoma (HNSCC). The primary study hypotheses are that IT MK-1454 in combination with pembrolizumab results in a superior Objective Response Rate (ORR), per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), compared to pembrolizumab alone: 1. in participants with a tumor that has a programmed cell death-ligand 1 (PD-L1) Combined Positive Scoring (CPS) ≥ 1, and 2. in participants with a tumor that has a PD-L1 CPS ≥ 20.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Intratumoral (IT) MK-1454 in Combination With Intravenous (IV) Pembrolizumab (MK-3475) Compared to IV Pembrolizumab Alone as the First Line Treatment of Metastatic or Unresectable, Recurrent Head and Neck Squamous Cell Carcinoma (HNSCC) (MK-1454-002)
  • Official Title: A Phase 2 Study in First Line Metastatic or Unresectable, Recurrent Head and Neck Squamous Cell Carcinoma to Evaluate Intratumoral MK-1454 in Combination With IV Pembrolizumab vs IV Pembrolizumab Monotherapy

Clinical Trial IDs

  • ORG STUDY ID: 1454-002
  • SECONDARY ID: 2019-003060-42
  • SECONDARY ID: MK-1454-002
  • NCT ID: NCT04220866

Conditions

  • Head and Neck Squamous Cell Carcinoma (HNSCC)

Interventions

DrugSynonymsArms
MK-1454MK-1454+Pembrolizumab
PembrolizumabMK-3475, KEYTRUDA®MK-1454+Pembrolizumab

Purpose

The purpose of this study is to assess the efficacy and safety of intratumoral (IT) MK-1454 in PLUS pembrolizumab (MK-3475) compared to pembrolizumab alone as a first line treatment of adults with metastatic or unresectable, recurrent head and neck squamous cell carcinoma (HNSCC). The primary study hypotheses are that IT MK-1454 in combination with pembrolizumab results in a superior Objective Response Rate (ORR), per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), compared to pembrolizumab alone: 1. in participants with a tumor that has a programmed cell death-ligand 1 (PD-L1) Combined Positive Scoring (CPS) ≥ 1, and 2. in participants with a tumor that has a PD-L1 CPS ≥ 20.

Trial Arms

NameTypeDescriptionInterventions
MK-1454+PembrolizumabExperimentalParticipants receive MK-1454 540 ug via intratumoral (IT) injection on Day 1 of every week for two 3-week cycles (Cycles 1-2), then on Day 1 of each 3-week cycle for up 33 cycles (Cycles 3-35), for a total of 35 cycles PLUS pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles. The total duration of treatment is up to approximately 2 years.
  • MK-1454
  • Pembrolizumab
PembrolizumabActive ComparatorParticipants receive pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for up to 35 cycles. The total duration of treatment is up to approximately 2 years.
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Has histologically or cytologically confirmed diagnosis of metastatic or unresectable,
             recurrent head and neck squamous cell carcinoma (HNSCC) that is considered incurable
             by local therapies

          -  Has tumor PD-L1 expression of CPS ≥1. Tumor tissue must be provided for PD-L1
             biomarker analysis

          -  Has not had prior systemic therapy administered in the recurrent or metastatic setting

          -  Has at least 1 measurable lesion which is amenable to injection

          -  Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

          -  Demonstrates adequate organ function within 7 days prior to treatment initiation

          -  Male participants of reproductive potential must agree to use a highly effective
             method of contraception during sexual contact with females of childbearing potential
             starting with the first dose of study treatment through 120 days after the last dose
             of study treatment

          -  Female participants of childbearing potential must be willing to use a highly
             effective method of birth control or be surgically sterile or abstain from
             heterosexual activity for the course of the study through 120 days after last dose of
             study treatment

          -  Human immunodeficiency virus (HIV)-infected participants must meet these additional
             criteria:

               1. Has HIV-1 infection documented by using any licensed rapid HIV test or HIV enzyme
                  or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study
                  entry (Day 1)

               2. Has well-controlled HIV on anti-retroviral therapy (ART)

        Exclusion Criteria:

          -  Has disease that is suitable for local therapy administered with curative intent

          -  Has progressive disease (PD) within 6 months of completion of curatively intended
             systemic treatment for locoregionally advanced HNSCC

          -  Has had chemotherapy or biological cancer therapy in the recurrent or metastatic
             setting for the treatment of HNSCC

          -  Has had radiation therapy (or other non-systemic therapy) within 2 weeks prior to
             randomization or participant has not fully recovered from adverse events (AEs) due to
             a previously administered treatment

          -  Is expected to require any other form of antineoplastic therapy while on study

          -  Has a history of a second malignancy, unless potentially curative treatment has been
             completed, with no evidence of malignancy for at least 2 years

          -  Has clinically active central nervous system (CNS) metastases and/or carcinomatous
             meningitis

          -  Has an active autoimmune disease that has required systemic treatment in the past 2
             years

          -  Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
             other form of immunosuppressive therapy within 7 days prior to the first dose of study
             treatment

          -  Has had an allogenic tissue/solid organ transplant

          -  Has a history of vasculitis

          -  Has a history of interstitial lung disease

          -  Has an active infection requiring systemic therapy

          -  Has a known history of active tuberculosis (TB; Bacillus tuberculosis)

          -  Has a history of (non-infectious) pneumonitis that required steroids or current
             pneumonitis

          -  Has had a severe hypersensitivity reaction to treatment a monoclonal
             antibody/components of the study treatment

          -  Has known Hepatitis B virus or Hepatitis C virus infections

          -  Has received prior therapy with an anti-programmed cell death 1 (anti-PD-1),
             anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-programmed cell death-ligand
             2 (anti-PD-L2) agent or if the participant has previously participated in Merck
             MK-3475 clinical trials

          -  HIV infected participant who has had an HIV-related opportunistic infection within 6
             months

          -  HIV infected participants who have a history of Kaposi's sarcoma and/or Multicentric
             Castleman's Disease

          -  Is pregnant, breastfeeding, or expecting to conceive or father children within the
             projected duration of the study, starting with the screening visit through 120 days
             after the last dose of study treatment

          -  Has not fully recovered from any effects of major surgery without significant
             detectable infection

          -  Has a history of re-irradiation for HNSCC at the projected injection site in the head
             and neck

          -  Has received a live-virus vaccine within 30 days of planned study treatment start

          -  Has been treated with a stimulator of interferon genes (STING) agonist (e.g. MK-1454,
             ADU-S100)

          -  Is currently participating and receiving study therapy or has participated in a study
             of an investigational agent and received study therapy, or used an investigational
             device, any of which occurred within 4 weeks of the first dose of study treatment
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Time Frame:Up to approximately 2 years
Safety Issue:
Description:ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. ORR will be assessed by blinded independent central review (BICR).

Secondary Outcome Measures

Measure:Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Time Frame:Up to approximately 2 years
Safety Issue:
Description:PFS is defined as the time from randomization to the first documented progressive disease (PD) or death from any cause, whichever occurs first. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. PFS will be assessed by blinded independent central review (BICR).
Measure:Duration of Response (DOR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Time Frame:Up to approximately 2 years
Safety Issue:
Description:DOR is defined as the time from the first documented evidence of a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 until Progressive Disease (PD) or death due to any cause, whichever occurs first, in participants demonstrating a CR or PR. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD.
Measure:Overall Survival (OS)
Time Frame:Up to approximately 2 years
Safety Issue:
Description:OS is defined as the time from randomization to the date of death from any cause.
Measure:Number of participants experiencing an Adverse Event (AE)
Time Frame:Up to approximately 2 years
Safety Issue:
Description:An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Measure:Number of participants discontinuing study treatment due to an Adverse Event (AE)
Time Frame:Up to approximately 2 years
Safety Issue:
Description:An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Merck Sharp & Dohme Corp.

Trial Keywords

  • Programmed Cell Death-1 (PD1, PD-1)
  • Programmed Death-Ligand 1 (PDL1, PD-L1)

Last Updated

April 16, 2020